This proposal examines the molecular genetic basis of the environmentally sensitive Hsp90 molecular chaperone buffered deformed eye (dfe) trait, which, like human diseases, fits a model of threshold traits. In aim 1, dissection of over 9 genetic regions involved in Drosophila Hsp90 buffering of dfe penetrance by deletion mapping and cDNA microarray analysis of transcription will deliver candidate genes and establish the genetic architecture of dfe. In aim two, the cloning of dfe genes will be unambiguously proved using site directed mutagenesis and transgenic complementation tests. Success of this program will enhance our understanding of the nature of genetic variation underlying complex traits, advance identification of genes involved in trait penetrance, and may establish connections between medically important Hsp90 signaling pathways and previously unidentified pathways providing novel candidate genes for common alleles affecting human disease. [unreadable] [unreadable]